Background and purpose: We aimed to assess the safety, feasibility, and effects on glucose metabolism of treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. Methods: We performed a multicenter, randomized, controlled, open-label phase II trial with blinded outcome assessment. Patients with TIA or minor ischemic stroke in the previous six months and impaired glucose tolerance (2-hour post-load glucose levels of 7.8-11.0mmol/l) were randomized to metformin, in a daily dose of 2g, or no metformin, for three months. Primary outcome measures were safety and feasibility of metformin, and the adjusted difference in 2-hour post-load glucose levels at three months. This trial is registered as an International Standard Randomized Controlled Trial Number 54960762. Results: Forty patients were enrolled; 19 patients were randomly assigned metformin. Nine patients in the metformin group had side effects, mostly gastrointestinal, leading to permanent discontinuation in four patients after 3-10 weeks. Treatment with metformin was associated with a significant reduction in 2-hour post-load glucose levels of 0·97mmol/l (95% CI 0·11-1·83) in the on-treatment analysis, but not in the intention-to-treat analysis (0·71mmol/l; 95% CI -0·36 to 1·78). Conclusions: Treatment with metformin in patients with TIA or minor ischemic stroke and impaired glucose tolerance is safe, but leads to minor side effects. If tolerated, it may lead to a significant reduction in post-load glucose levels. This suggests that the role of metformin as potential therapeutic agent for secondary stroke prevention should be further explored.

Antidiabetics, Impaired glucose tolerance, Ischemic stroke, Metformin, Secondary stroke prevention, TIA,
International Journal of Stroke
Department of Neurology

den Hertog, H.M, Vermeer, S.E, Zandbergen, A.A.M, Achterberg, S, Dippel, D.W.J, Algra, A, … Koudstaal, P.J. (2015). Safety and feasibiLIty of Metformin in patients with Impaired glucose Tolerance and a recent TIA or minor ischemic stroke (LIMIT) trial - a multicenter, randomized, open-label phase II trial. International Journal of Stroke, 10(1), 105–109. doi:10.1111/ijs.12023